Pancreatic cancer is one of the most difficult cancers to combat with less than 5% 5 year survival and less than 1 year median survival rates [Xu, J. et al. Cancer statistics, 2007. CA Cancer J Clin 57:43-66]. Despite intense global efforts, curing this dreaded disease remains a formidable challenge. Recent studies using genetically engineered mouse model revealed Plectin-1 (Plec1) as a potential novel imaging biomarker for pancreatic duct adeno carcinoma PDAC. Effective diagnosis and treatment of cancer critically depends on developing tumor or tumor vasculature specific delivery of diagnostic markers/cytotoxic cancer drugs (Shukla, G. S. et al. Expert. Opin. Biol. Ther. 2006; 6:39-54). To this end, potent cytotoxic drugs are often selectively delivered to tumor cells or tumor endothelial cells via receptors over expressed on tumors/tumor vasculatures (Vyas, S. P. et al. Crit. Rev. Ther. Drug Carrier Syst. 2001; 18:1-76). Prior studies reported that KTLLPTP(SEQ ID NO: 3) is a high affinity ligand for Plec1 [Kelly et al. (2008] Targeted nanoparticle for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med 5:4:e85; Interactional Pat. Pub. No. WO 2009/129220, Kelly et al., published Oct. 22, 2009; WO2011057078-A2; WO2011057078-A3; CA2779730-A1; AU2010315021-A1; ˜US2012219499-A1; EP2496948-A2; KR2012101054-A; CN102762984-A; JP2013510094-W; WO2009129220-A2; ˜WO2009129220-A3; EP2265630-A2; JP2011521897-W; US2011182814-A1; CA2758415-A1]. These latter inventions disclose compositions and methods useful for diagnostic and imaging techniques for detecting and localizing the biomarker Plectin-1. The inventions disclose multimeric peptide ligand complexes (ssAKTLLPTPGGS (PEG5000)) 4 KKKKDOTAssA-NH2 ([(pAla-Lys-Thr-Leu-Leu-Pro-Thr-Pro-Gly-Gly-Ser-PEG5K) 2-Lys] 2-Lys-Lys (DOTA)-pAla-NH2 (SEQ ID NO: 5)) to which imaging agents and/or therapeutic agents were conjugated) for targeting to Plectin-1. Lee et al. disclosed methods for preparation of lipid-hydrophilic polymer-reactive functional group-peptide (DSPE(SEQ ID NO: 6)-PEG-octreotide) and delivering anticancer drugs to pancreatic tumor (US2008102110-A1; JP2008115147-A; TW200819137-A; TW362270-B1). Additional prior arts related to targeting drugs to pancreatic tumors include: Targeted Drug Delivery in Pancreatic Cancer by Yu et al. (Biochim Biophys Acta., 2010, 1805(1), 97-104) and Plectin-1 as a Novel Biomarker for Pancreatic Cancer by Bausch et al. (Clin Cancer Res; 17(2); 302-9).
Genetic immunization (DNA vaccination, the administration of tumor antigen encoded DNA) is an emerging therapeutic approach for treatment of cancer. This therapeutic modality is capable of inducing both humoral and cellular immune responses against tumor (Ishii, K. J. et al. Nature 2008; 451:725-729, Gurunathan, S. et al. Annu. Rev. Immunol. 2000; 18:927-974). Efficient DNA vaccination requires targeting DNA vaccines to recipients' antigen present cells (APCs). To this end, mannose receptor, a 180 kDa multi-domains unique transmembrane receptor over expressed on the cell surfaces of APCs (Sallusto, F. et al. J. Exp. Med. 1995; 182:389-400) are finding increasing exploitations (Lu, Y. et al. Biomaterials, 2007, 28, 3255-3262; P.-L. Jiang et al. Acta Biomaterialia 2015, 11, 356-367; Wijagkanalan, W. et al. J. Controlled. Release. 2008, 125, 121-130). Srinivas, R. et al. demonstrated for the first time that liposomes of cationic amphiphiles with mannose-mimicking quinoyl- and shikimoyl-head-groups can target DNA vaccines to APCs via mannose receptors more efficiently than their mannosyl counterparts (Srinivas, R. et al. J. Med. Chem. 2010; 53:1387-1391). Subsequently, Srinivas, R. et al. disclosed more efficacious mannose receptor specific lysinylated cationic amphiphiles with mannose-mimicking shikimoyl- and quinoyl-head-groups for use in ex vivo (outside the body cells) dendritic cell (DC, the most professional antigen presenting cells) transfection based genetic immunization (Srinivas, R. et al. Biomaterials 2012, 33, 6220-6229, International Patent Application No. PCT/IN2011/000629; Indian Patent Application No. 2170/DEL/2010). However, such ex vivo DC-transfection based DNA vaccination methods suffer from a number of time-consuming and cost-ineffective steps including painstaking isolation of autologous DCs, transfecting them ex vivo with tumor antigen encoded DNA vaccines and reimplanting the ex vivo transfected DCs back into the recipient's body. To this end, Hashida and coworkers reported development of mannose-receptor selective and ultrasound-responsive mannosylated liposomes for direct in vivo transduction of DCs in genetic immunization (Un K. et al. Biomaterials 2010; 31: 7813-7826; Un K. et al. Mol Pharm 2011; 8: 543-554). Garu, A. et al. has recently developed an efficient method for direct in vivo targeting of DNA vaccines using novel liposomal DNA vaccine carriers (Indian Patent Application No. 0017/DEL/2013). Although inhibiting growth of melanoma tumor in mice priorly immunized with such direct in vivo DC-targeting liposomal DNA vaccine formulation was possible, this approach failed to regress established tumor. Potent targeted cancer therapeutics is often associated with multidrug resistance (MDR), acute toxicities, cumulative dose-limiting cytoxicity, etc. Thus, there is an urgent need to use combination of targeted chemotherapy and in vivo DC-targeted tumor antigen encoded DNA vaccination for regressing established tumors (Szakacs, G. et al. Nat. Rev. Drug Discov. 2006; 5:219-234).